This proposed research is specifically aimed at total syntheses of rifamycin-S, maytanacine, and streptovaricine-D, each representing three major subgroups of ansamycins. Of many remarkable physiological properties these antibiotics exhibit, their antitumor and antileukemic activities are particularly notable. While maytansine (an analogue of maytanacine) is currently undergoing Phase II of clinical studies, the others are regarded as promising potential antitumor agents. The ansamycins have the unique structural feature that an aliphatic bridge (ansa bridge) spans across two non-adjacent positions of a monocyclic or bicyclic aromatic nucleus. Therefore the synthesis of these molecules invovles three distinct stages: (1) the construction of the ansa bridge which is highly oxygenated and rich in chirality, (2) that of the aromatic nucleus, and finally, (3) the combination of these two major fragments to form a macromonocyclic lactam. Our recent discovery of the boron-mediated aldol condensation has solved a major stereochemical problem of this reaction, and it is hoped that the proposed additional work will provided answers to the problems associated with the construction of the ansa chain. The synthesis of the aromatic portion appears to be feasible by a judicious combination of known organic reactions. Many devices for the lactam formation can be made with our experience in macrolide synthesis and also with accumulated literature of peptide bond formation. It should be added that the synthetic methodology we propose to develop is designed to be generally applicable for a variety of stereochemical combinations conceivable for the ansa chain. Thus the synthesis of unnatural antibiotics modified in this apparently important portion of the molecules will, in principle, become possible if a need to prepare such compounds arises for biological screening.